Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Mar 1;181(3):1179–1186. doi: 10.1084/jem.181.3.1179

P-selectin and vascular cell adhesion molecule 1 mediate rolling and arrest, respectively, of CD4+ T lymphocytes on tumor necrosis factor alpha-activated vascular endothelium under flow

PMCID: PMC2191919  PMID: 7532680

Abstract

This report examines the adhesive interactions of human CD4+ T lymphocytes with tumor necrosis factor alpha-activated human endothelial cell monolayers in an in vitro model that mimics microcirculatory flow conditions. Resting CD4+ T cell interactions with activated endothelium consisted of initial attachment followed by rolling, stable arrest, and then spreading and transendothelial migration. P-selectin, but not E-, or L-selectin, mediated most of this initial contact and rolling, whereas beta 1-integrins (alpha 4 beta 1), interacting with endothelial-expressed vascular cell adhesion molecule 1, participated in rolling and mediated stable arrest. In contrast, beta 2-integrins were primarily involved in spreading and transmigration. These findings highlight an important role for P- selectin and suggest discrete functions for beta 1- and beta 2- integrins during lymphocyte recruitment to sites of immune-mediated inflammation.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbassi O., Kishimoto T. K., McIntire L. V., Anderson D. C., Smith C. W. E-selectin supports neutrophil rolling in vitro under conditions of flow. J Clin Invest. 1993 Dec;92(6):2719–2730. doi: 10.1172/JCI116889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bargatze R. F., Butcher E. C. Rapid G protein-regulated activation event involved in lymphocyte binding to high endothelial venules. J Exp Med. 1993 Jul 1;178(1):367–372. doi: 10.1084/jem.178.1.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bjerknes M., Cheng H., Ottaway C. A. Dynamics of lymphocyte-endothelial interactions in vivo. Science. 1986 Jan 24;231(4736):402–405. doi: 10.1126/science.3941903. [DOI] [PubMed] [Google Scholar]
  5. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  6. Doré M., Korthuis R. J., Granger D. N., Entman M. L., Smith C. W. P-selectin mediates spontaneous leukocyte rolling in vivo. Blood. 1993 Aug 15;82(4):1308–1316. [PubMed] [Google Scholar]
  7. Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grober J. S., Bowen B. L., Ebling H., Athey B., Thompson C. B., Fox D. A., Stoolman L. M. Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions. J Clin Invest. 1993 Jun;91(6):2609–2619. doi: 10.1172/JCI116500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Issekutz T. B. Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivity-induced inflammation. Am J Pathol. 1993 Nov;143(5):1286–1293. [PMC free article] [PubMed] [Google Scholar]
  10. Issekutz T. B. Inhibition of lymphocyte endothelial adhesion and in vivo lymphocyte migration to cutaneous inflammation by TA-3, a new monoclonal antibody to rat LFA-1. J Immunol. 1992 Nov 15;149(10):3394–3402. [PubMed] [Google Scholar]
  11. Juliano R. L., Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. doi: 10.1083/jcb.120.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kunzendorf U., Notter M., Hock H., Distler A., Diamantstein T., Walz G. T cells bind to the endothelial adhesion molecule GMP-140 (P-selectin). Transplantation. 1993 Nov;56(5):1213–1217. doi: 10.1097/00007890-199311000-00031. [DOI] [PubMed] [Google Scholar]
  13. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  14. Lawrence M. B., Springer T. A. Neutrophils roll on E-selectin. J Immunol. 1993 Dec 1;151(11):6338–6346. [PubMed] [Google Scholar]
  15. Ley K., Gaehtgens P., Fennie C., Singer M. S., Lasky L. A., Rosen S. D. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed] [Google Scholar]
  16. Lorant D. E., Patel K. D., McIntyre T. M., McEver R. P., Prescott S. M., Zimmerman G. A. Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol. 1991 Oct;115(1):223–234. doi: 10.1083/jcb.115.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Luscinskas F. W., Cybulsky M. I., Kiely J. M., Peckins C. S., Davis V. M., Gimbrone M. A., Jr Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. J Immunol. 1991 Mar 1;146(5):1617–1625. [PubMed] [Google Scholar]
  18. Luscinskas F. W., Kansas G. S., Ding H., Pizcueta P., Schleiffenbaum B. E., Tedder T. F., Gimbrone M. A., Jr Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins. J Cell Biol. 1994 Jun;125(6):1417–1427. doi: 10.1083/jcb.125.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mayadas T. N., Johnson R. C., Rayburn H., Hynes R. O., Wagner D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. doi: 10.1016/0092-8674(93)80055-j. [DOI] [PubMed] [Google Scholar]
  20. Muller W. A., Weigl S. A., Deng X., Phillips D. M. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993 Aug 1;178(2):449–460. doi: 10.1084/jem.178.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  22. Rice G. E., Munro J. M., Bevilacqua M. P. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. doi: 10.1084/jem.171.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sako D., Chang X. J., Barone K. M., Vachino G., White H. M., Shaw G., Veldman G. M., Bean K. M., Ahern T. J., Furie B. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993 Dec 17;75(6):1179–1186. doi: 10.1016/0092-8674(93)90327-m. [DOI] [PubMed] [Google Scholar]
  24. Shen J., Luscinskas F. W., Connolly A., Dewey C. F., Jr, Gimbrone M. A., Jr Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells. Am J Physiol. 1992 Feb;262(2 Pt 1):C384–C390. doi: 10.1152/ajpcell.1992.262.2.C384. [DOI] [PubMed] [Google Scholar]
  25. Shimizu Y., Newman W., Gopal T. V., Horgan K. J., Graber N., Beall L. D., van Seventer G. A., Shaw S. Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol. 1991 Jun;113(5):1203–1212. doi: 10.1083/jcb.113.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  27. Smith C. W., Kishimoto T. K., Abbassi O., Hughes B., Rothlein R., McIntire L. V., Butcher E., Anderson D. C., Abbass O. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J Clin Invest. 1991 Feb;87(2):609–618. doi: 10.1172/JCI115037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spertini O., Luscinskas F. W., Kansas G. S., Munro J. M., Griffin J. D., Gimbrone M. A., Jr, Tedder T. F. Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J Immunol. 1991 Oct 15;147(8):2565–2573. [PubMed] [Google Scholar]
  29. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  30. van Seventer G. A., Newman W., Shimizu Y., Nutman T. B., Tanaka Y., Horgan K. J., Gopal T. V., Ennis E., O'Sullivan D., Grey H. Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med. 1991 Oct 1;174(4):901–913. doi: 10.1084/jem.174.4.901. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES